β-Elemene Reverses Chemoresistance of Breast Cancer via Regulating MDR-Related MicroRNA Expression
| Autor: | Jun Zhang, He da Zhang, Lin Chen, Da Wei Sun, Chang fei Mao, Wei Chen, Jian Zhong Wu, Shan liang Zhong, Jian Hua Zhao, Jin Hai Tang |
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| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: | |
| Zdroj: | Cellular Physiology and Biochemistry, Vol 34, Iss 6, Pp 2027-2037 (2014) |
| Druh dokumentu: | article |
| ISSN: | 1015-8987 1421-9778 |
| DOI: | 10.1159/000366398 |
| Popis: | Background: Multidrug resistance (MDR) directly contributes to the clinical failure of chemotherapy in breast cancer (BCA). β-elemene is a natural antitumor drug from plants. We previously confirmed that MDR could be reversed by β-elemene. In this study, we intended to investigate the reversal effect of β-elemene on MDR in human BCA adriacin (Adr) -resistant MCF-7 cells (MCF-7/Adr) and docetaxel (Doc) - resistant MCF-7 cells (MCF-7/Doc) through the gene regulatory network. Methods: MTT-cytotoxic, miRNA microarray, Real-time quantitative PCR, Dual Luciferase Activity Assay, Western blot analysis were performed to investigate the impact of β-elemene on chemo-resistant BCA cell suvival, and its impact on the expression of chemo-resistance specific miRNA and the downstream target genes PTEN and Pgp. Results: Compared with the miRNAs expression profiles of MCF-7/Adr and MCF-7/Doc cell lines from our previous studies, there were 322 differentially expressed miRNAs in MCF-7/Adr and MCF-7/Doc breast cancer cells with β-elemene intervention (50μM/L) for 30h, and 6 miRNAs were significantly up-regulated and 12 miRNAs were significantly down-regulated in both MCF-7/Adr and MCF-7/Doc. We have testified that 5 miRNA is related to MDR before, in this study, the expression of miR-34a, miR-222, miR-452 and miR-29a can lead to changes of the characteristics of chemo-resistant MCF-7/Adr and MCF-7/Doc. The PTEN expression under intervention of β-elemene was significantly increased and Pgp expression under β-elemene intervention was significantly decreased in both cell lines. Conclusions: β-elemene could influence MDR related miRNA expression and subsequently regulate the expression of the target genes PTEN and Pgp, which may lead to reduction of the viability of the chemo-resistant breast cancer cells. |
| Databáze: | Directory of Open Access Journals |
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